GeneBe

HYLS1

HYLS1 centriolar and ciliogenesis associated

Basic information

Region (hg38): 11:125883614-125900646

Links

ENSG00000198331 ∙ NCBI:219844 ∙ OMIM:610693 ∙ HGNC:26558 ∙ Uniprot:Q96M11 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • hydrolethalus syndrome 1 (Definitive), mode of inheritance: AR
  • hydrolethalus syndrome 1 (Strong), mode of inheritance: AR
  • Joubert syndrome (Supportive), mode of inheritance: AR
  • hydrolethalus syndrome (Supportive), mode of inheritance: AR
  • hydrolethalus syndrome 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Hydrolethalus syndromeARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Pulmonary7028327; 15843405; 18648327

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HYLS1 gene.

  • not_provided (222 variants)
  • Inborn_genetic_diseases (103 variants)
  • Hydrolethalus_syndrome (49 variants)
  • Hydrolethalus_syndrome_1 (23 variants)
  • Severe_growth_deficiency-strabismus-extensive_dermal_melanocytosis-intellectual_disability_syndrome (15 variants)
  • PUS3-related_disorder (7 variants)
  • not_specified (3 variants)
  • Anencephaly (2 variants)
  • Aplasia/Hypoplasia_of_the_cerebellum (2 variants)
  • Genetic_syndrome_with_a_Dandy-Walker_malformation_as_major_feature (2 variants)
  • Polyhydramnios (2 variants)
  • Dandy-Walker_syndrome (2 variants)
  • Ankle_flexion_contracture (2 variants)
  • Heart,_malformation_of (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HYLS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001134793.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
117
clinvar
1
clinvar
 120
missense
1
clinvar
49
clinvar
2
clinvar
1
clinvar
 53
nonsense
9
clinvar
1
clinvar
 10
start loss
0
frameshift
4
clinvar
2
clinvar
 6
splice donor/acceptor (+/-2bp)
0
Total 1 13 54 119 2

Highest pathogenic variant AF is 0.000621345

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
HYLS1protein_codingprotein_codingENST00000425380 117035
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
2.32e-90.1461256750731257480.000290
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.1771611670.9620.000009431932
Missense in Polyphen5060.8060.82229664
Synonymous0.1475556.40.9750.00000263606
Loss of Function0.2981415.30.9180.00000118136

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0009110.000911
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.00004620.0000462
European (Non-Finnish)0.0003080.000308
Middle Eastern0.00005440.0000544
South Asian0.0002610.000261
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Plays a role in ciliogenesis. {ECO:0000250|UniProtKB:A0A1L8ER70, ECO:0000250|UniProtKB:Q95X94}.;
Disease
DISEASE: Hydrolethalus syndrome 1 (HLS1) [MIM:236680]: A lethal syndrome characterized by polydactyly, central nervous system malformation, and hydrocephalus. The polydactyly is postaxial in the hands and preaxial in the feet. A highly characteristic hallux duplex is seen in almost no other situation. In half of the cases, a large atrioventricular communis defect of the heart is found. The pregnancy is characterized by hydramnios, which is often massive, and by preterm delivery. {ECO:0000269|PubMed:15843405}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in HYLS1 may be involved in ciliopathies other than hydrolethalus syndrome 1. A homozygous mutation resulting in a C-terminal extension of 11 residues has been found in patients diagnosed as Joubert syndrome, a ciliopathy presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. {ECO:0000269|PubMed:26830932}.;

Recessive Scores

pRec
0.167

Intolerance Scores

loftool
0.565
rvis_EVS
-0.03
rvis_percentile_EVS
51.66

Haploinsufficiency Scores

pHI
0.115
hipred
N
hipred_score
0.144
ghis
0.524

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
S
essential_gene_gene_trap
H
gene_indispensability_pred
E
gene_indispensability_score
0.752

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Hyls1
Phenotype

Gene ontology

Biological process
cilium assembly
Cellular component
nucleus;cytoplasm;centrosome;centriole;cytosol;plasma membrane;cilium;non-motile cilium
Molecular function
protein binding